- Email: [email protected]
Human V4?
COLOUR
WILLIAM H. MERIGAN
VISION
Human V4? Lesion studies of the macaque and human visual cortices again fail to demonstrate a simple parallel between the two. A recent article by Heywood
et al. [l] has emphasized just how difftcult it is to compare the visual cortices of humans and macaques, This comparison has become very important in recent years as our knowledge of human and macaque cortices has grown immensely but without the kind of bridging observations that could link them. Many investigators now feel that a real understanding of the primate visual cortex requires that these two data sets be joined.
Human studies have always been important in understanding vision because a wealth of data has been obtained from detailed psychophysical examination of human subjects, on everything from color vision to visual cues for shape perception. Unfortunately, although this enormous literature shows us in detail the capabilities of the visual system, it is only of limited use as a guide to how this particular skill might be accomplished. There are two types of evidence, however, which have come only from humans, and that offer a strong possibility of uncovering the structure underlying human visual processing. The first is the observation that humans with localized brain lesions can have extraordinarily selective impairments of low level visual functions. Some of the most dramatic losses are in motion perception [Z], a deficit sometimes termed akinetopsia, in face recognition, a loss termed prosopagnosia [3], and in color vision, the loss of which is called achromatopsia [4]. These visual effects are surprising in that they are often quite specific (for example, achromatopsia can occur without any marked deficit in achromatic vision), and they seem quite permanent. These are exactly the qualities that would lead us to the suspect that the visual cortex may have localized, function-specific processing and that other healthy parts of the brain cannot assume the lost functions. Indeed, such lesion-induced visual loss has become a major part of the argument that the brain functions in a modular fashion. The second result from humans also strengthens our belief in localized visual cortical processing. Functional imaging studies of the human brain during vision, initially with positron emission tomography (PET) and more recently with magnetic resonance imaging (MN), have suggested that there are local ‘hot spots’ of neural activity, which can be found in slightly different cortical locations depending on the type of visual stimuli. For instance, hot spots evoked by color stimulation are in a different location from those evoked by visual motion stimulation. And perhaps most interestingly, the location of the hot spot found during color stimulation is close to the brain area in which localized lesions cause achromatopsia [ 561, whereas the hot spot produced by visual motion stimulation is close to @ Current
Biology
the region implicated in motion deficits 161. These results, and others like them, suggest that there is some regional specialization of the human visual cortex for such dimensions as color, motion, and face recognition. Although these advances are exciting, there remains a general consensus that human studies of cortical localization leave a lot to be desired - because virtually nothing is known about the connectional anatomy and single cell physiology of human cortex (nor is it likely that this will change), and because human cortical lesions are hopelessly clumsy: they are not confined to known structures, are not made with axon-sparing methods, and cannot involve ‘pre’ and ‘post’ comparisons in which measurements are taken from normal tissue before the lesion occurs, AI-I obvious solution to these problems is to compare these findings from humans with the wealth of experimental data from non-human primates, primarily macaque monkeys. Indeed, the macaque monkey offers just the sort of information that is not available for human visual cortex. Macaque cortex has been mapped connectionally [7] in somewhat dizzying detail. What is more, there is a great wealth of data from recording single neurones that can be used to flesh out anatomical maps. Beyond these obvious advantages, macaques offer many sorts of experimental information that are not even potentially available from humans - studies of the effects on the developing visual system of rearing in visually restricted environments, current source density analysis (the study of sources and sinks of electrical activity in the brain), and deoxyglucose mapping of metabolically active areas, to name a few. All of these information sources would become very useful if the macaque could be shown to be an informative model for the function of the human visual system. As might be expected, given the potential benefits, the literature is rich with proposed parallels between macaque and human visual cortices. One of the first similarities to be suggested, and one that continues to arouse speculation, is between the regions involved in the processing of visual motion - a small myelinated region of lateral human cortex and a region of the macaque extrastriate area known as MT. This match relies, on the human side, on functional imaging of the hot spot in the brain found with visual motion stimulation and the locus of brain lesions that cause deficits in human motion perception, On the macaque side, the physiological properties of MT neurons are motion-dominated and a deficit in macaque motion perception is caused by MT lesions. This proposed match is the most plausible of those suggested to date, but many investigators think that even this parallel will prove ephermeral. 1993,
Vol 3 No 4
DISPATCH
Macaque
Sagittal
Human
-----
Transverse
Fig. 1. Coronal, sagittal and transverse views of the brains of macaque (left) and human (right). The two brains are shown at different magnifications as the human brain is much larger. In the maca ue brain, the mid-blue regions indicate the extent of area V4, all of which was iesiones in V4 in the study of Heywood et al., [I]. The 1 ark blue region shows the site of a more restricted V4 lesion that can be used when fixation locus is controlled during visual testing (e.g. in the study of Schiller and Lee, [Ill). In the human brain, the three views illustrate in red the locus of the imaging hot spot found by Zeki et al. [61 in response to color-varying visual stimulation, The locus of lesions that result in cerebral achromato sia [4] are indicated in mid-blue and can only be estimated as there are no anatomical data for this part of the human brain that coul dpsuggest a candidate area for V4.
A more recent match, on which I shall focus, and on which the Heywood et al. [l] paper casts some light, is the ‘human V4’ proposal, This terminology reflects the attempt to combine macaque single-unit physiology from area V4 with human achromatopsia, in order to
deftne a single area in the visual cortexof these two primates that is central to the visual processing of color, The investigator most identified with this approach is Semir Zeki of University College, Iondon, who has conducted many of the physiological studies that have ledto the identification
227
228
Current
Biology
1993, Vol 3 No 4
of macaque ~4 as a color-specialized area. Perhaps his most dramatic iindings have concerned the response of neurons in V4, not to the wavelength (actual color) of the stimuli, but to their ‘contextual color’ when presented within an array of colored patches 181. Humans, like single neurons in macaques, respond to colors in a contextual or opponent fashion (i.e responding to the difference between a color and its background), suggesting that this neuronal response may be particularly critical for color perception. Zeki has proposed that the relatively specific decolorization of the visual world found in cerebral achromatopsia may result from damage to the human counterpart of the cortical area V4 in the macaque [4]. In the study by Heywood et al. [ 11, a broad range of visual abilities, with particular emphasis on color vision, was tested in three macaques before and after bilateral lesions were made in cortical area V4 (Fig. 1). This was not the first time that macaques have been tested visually after ~4 lesions. At least four groups have published such studies [!+12], and the general consensus that has emerged from this work is that macaques retain rather good color vision after ~4 lesions. Unfortunately, one cannot ask these monkeys if the world appears decolorized, one of the major changes reported by human achromatopsics, but it should be possible to see if they show the same color threshold losses as their human counterparts. What was most interesting about the recent Heywood et al. [ 1] study was that it was designed to see if macaques without V4 had similar deficits to those found in the color vision of a human achromatopsic they had previously examined [ 131. The most striking loss in their achromatopsic patient (and in many previously reported patients) was in his ability to make color-discriminations, shown most drastically by his abysmal performance on a color sorting task, known as the FarnsworthMunsell loo-Hue Test, with 13 mm desaturated (i.e. pale) color caps. The patient’s poor performance was also repeated in ordering and oddity discrimination tasks with larger color patches, and with color patches of graded saturation. Heywood and colleagues then adapted the stimuli of this study to test the color vision of their monkeys after lesions in the V4 region. Unlike the human patient, the monkeys showed excellent performance on the threechoice oddity tasks for color discrimination. They were also able to do two tasks that required the discrimination of ordered from disordered series of colored patches, al though they made a moderate number of errors before reaching the ‘85% correct’ performance criterion. Unfortunately, the authors were unable to train the experimental and control monkeys on an additional ordering task, designed as an analogue of the Farnsworth-Munsell Test, in which the color patches were separated by an achromatic background. However, despite this limitation on the monkey-human comparison, this study shows quite convincingly that monkeys with V4 lesions show little or no impairment on color-discrimination tasks that are impossible for a human achromatopsic. This study strengthens the emerging conclusion that in color vision, as in motion perception and in visual neglect, macaques with cortical lesions do not seem to show
the profound and enduring visual loss found in some humans. To be sure, there are persistent effects of cortical lesions in macaques, such as marginal abnormalities in eye movements, slight limitations in texture perception, and increases in the number of trials needed to learn form discriminations. However, none of these is as fundamental or as dramatic as the color vision and motion perception weaknesses of human patients. An important difference may be the extent to which the lesions are localized. In many human cases, the damage appears to extend well below the cortical mantle and deep into the fiber tracts underlying the grey matter. Of course, some experimental lesions made in macaques also damage white matter, if they are not produced with an axon-sparing toxicant such as ibotenic acid. But such damage usually does not extend as deep into white matter as that caused by strokes or the excision of epileptic foci. Whether or not a different location is the basis, however, the lack of permanent and dramatic visual losses seen in experimental macaques does not support the notion of specific, modular processing units in primate visual cortex. On the other hand, as pointed out above, imaging studies in humans show local hot spots of cortical activity in response to color or visual motion stimulation. Is this not strong evidence of localized cortical processing? It certainly appears to suggest modular function, especially if the hot spots are located in regions of cortical grey matter that might correspond to visual areas in the macaque. Even so, it is not clear that the hot spots are well placed to correspond to visual areas. For exam ple, in a recent study [6] of a hot spot responsive to color stimulation, the focus of activity was found sufficiently distant from the cortical surface that it might be in the white matter (Fig. l), although one cannot be certain, given that the sulcal fold pattern in these subjects is not known. Is this a matter of slight mislocalization of the hot spot, or an indication that it is not the cortical areas themselves that show specialization but rather regions of intracortical connection? A second concern is that the hot spots are the result of image processing, which could turn simple, intensive non-linearities in signal distribution into apparently local ized activity. Many cortical areas are active during visual stimulation, but this general activity is removed by the subtraction of activity that is common to other forms of stimulation from that due to the stimulation of interest. Thus, the colorful areas pinpointed in these studies are the areas that show increased activity during particular types of visual stimulation relative to other types of visual stimulation, One would expect that the activity in the marked areas increases more than that in other regions, but this is not necessarily the case. If there were an accelerating, non-linearity in the function relating cortical activity to the amount of PET or MRI signal (that is, if there were a selective amplification of high signals relative to the background activity), then subtraction would highlight regions of peak activity but would not indicate how widespread the regions were. Of course, this type of widespread pattern might be exactly what we would expect of even a modularly organized visual cortex, as multiple modules might be simultaneously activated by
DISPATCH
many types of stimulation. The greater difhculty is to be certain that this is not the response signature of a cortex with a more distributed representation of visual function. It is of some concern that even if the cortex had a non-modular organization, hot spots might be created by subtraction of images taken with and without stimulation. Finally, if macaque and human cortices are not organized differently, one is left with the difhculty of understanding how humans could lose particular visual functions af ter naturally occurring cortical lesions. Two possibilities come to mind. The first is that there could be greater selectivity to lesions in the visual cortex than is suggested by their position rather deep within the cortex. Selectivity, despite this deep location, could come about if there were some special vulnerability of particular neural elements, for example sensitivity of finer axons, transmitter-specific ischaemic damage and specific effects on certain receptor types, or even fortuitous damage to specialized axon bun dles passing through a region. This speculation recalls the well established observation that orientation-specific loss of contrast sensitivity can be caused by multiple sclerosis, a disease that affects axonal myelin [ 141, and that this peculiar visual loss most likely reflects damage in the visual cortex - the region in which orientation specificity is first found in macaques. A less attractive possible explanation of function-specific loss after human cortical lesions is that the cortical damage may be truly random but that in some cases non-specific damage may result in very specific visual loss. A possible example is the intriguing case of a rather specific inability to perform visually guided movements following probably widespread brain damage from carbon monoxide poisoning [ 151. The next few years are likely to bring advances in imaging techniques, further studies of humans with cortical lesions, and continued experimental studies with macaques, like those of Heywood and colleagues [l,lO] , which may bring the human and macaque findings into register. Until then, the description of human V4 must remain more hypothesis than conclusion. References 1. HI??OOD
CA
GAXXTI
A, COWEY
A Cortical
area
V4 and
its
role
2.
in the perception
of color.
J Neurosci
229
1992, 12:40564065. of movedamage Brain 1991,
ZIHL J, VON CRAMPON D, MAI N, SCH~UD CH: Disturbance
ment
vision
after
bilateral
posterior
brain
114:223$2252. 3. 4. 5.
AR, DAMA%O H, VAN HOESEN GW: anatomic basis and behavioral mechanisms 32:331-341. ZEKI S: A century of cerebral achromatopsia 1131721-1777. CORSE’ITA M, MIFXN
ZEKI
S, WA’IXON
8. 9. 10.
Bruin
1998,
attention during speed: functional / Neurasci 1991,
JDG,
LUECK
CJ,
visual discriminations anatomy by positron 11:2383-2402.
FFUSTON
KJ,
KENNARD
C,
RSJ: A direct
demonstration of functional specialization in human visual cortex. J Neurasci 1991, 11:641&9. FELLEMAN DJ, VAN ESSEN DC: Distributed hierarchical processing in the primate cerebral cortex. Cerebral Cortex 1991, 1:147. ZEKI S: Colour coding in the cerebral cortex: the reaction of cells in monkey visual cortex to wavelengths and colours. Neumcience 1983, 9741-765. DEAN P: Visual cortex ablation and thresholds for successively presented stimuli in rhesus monkeys: II. Hue. Exp Bruin Res 1991, 35:6%33. FRACKOWIAK
7.
Neurohgy
FM, DOBMEY!ZR S, SHULMAN GL, PETEF~EN SE:
Selective and divided of shape, color, and emission tomography
6.
Prosopagnosia 1982,
DAMA%O
HEYw~OD
the
CA,
COWEY
discrimination
A: On
of hue
the
role
and pattern
of
cortical
in macaque
area
V4
in
monkeys.
J Neurosci 1987, 7:2601-2617. 11.
SCHILLER PH,
V4 in vision. 12.
13.
14.
LEE K: The role of the primate Science 1991, 251:1251-1253.
area
JJ, BUTLER SR, CARDEN D: The effects of lesions of area V4 on the visual abiities of macaques: colour categorization Rehav Brain Res 1992, 7:1-9. ~nvOoD CA, WrrSON B, COWEY A A case study of cortical colour ‘blindness’ with relatively intact achromatic discrimination. J Neural Neurosurg Psychiatry 1987, 50:22-29. KEGAN DM, WHITUXK J, MURRAY TJ, B!ZVEKLEX KI: Orientationspecific losses of contrast sensitivity in multiple sclerosis. In-
WALSH V, KULIKOWSKI
vest Ophtbalmol Vis Sci 15.
extrastriate
1980,
19:324-328.
MILNER AD, PERRETT IX, JOHNSTON RS, BENSON PJ, JORDAN TR, HEELEY DW, BEITLICCI D, MORTARA F, MUTANI R, TERAZII E, DAVIDSON DLW: Perception and action in visual form agnosia Rrain 1991, 114:405-428.
-
William H. Merigan, Department of Ophthalmology and Center for Visual Science, Box 314, University of Rochester, Rochester, NY 14642, USA
WILLIAM H. MERIGAN
VISION
Human V4? Lesion studies of the macaque and human visual cortices again fail to demonstrate a simple parallel between the two. A recent article by Heywood
et al. [l] has emphasized just how difftcult it is to compare the visual cortices of humans and macaques, This comparison has become very important in recent years as our knowledge of human and macaque cortices has grown immensely but without the kind of bridging observations that could link them. Many investigators now feel that a real understanding of the primate visual cortex requires that these two data sets be joined.
Human studies have always been important in understanding vision because a wealth of data has been obtained from detailed psychophysical examination of human subjects, on everything from color vision to visual cues for shape perception. Unfortunately, although this enormous literature shows us in detail the capabilities of the visual system, it is only of limited use as a guide to how this particular skill might be accomplished. There are two types of evidence, however, which have come only from humans, and that offer a strong possibility of uncovering the structure underlying human visual processing. The first is the observation that humans with localized brain lesions can have extraordinarily selective impairments of low level visual functions. Some of the most dramatic losses are in motion perception [Z], a deficit sometimes termed akinetopsia, in face recognition, a loss termed prosopagnosia [3], and in color vision, the loss of which is called achromatopsia [4]. These visual effects are surprising in that they are often quite specific (for example, achromatopsia can occur without any marked deficit in achromatic vision), and they seem quite permanent. These are exactly the qualities that would lead us to the suspect that the visual cortex may have localized, function-specific processing and that other healthy parts of the brain cannot assume the lost functions. Indeed, such lesion-induced visual loss has become a major part of the argument that the brain functions in a modular fashion. The second result from humans also strengthens our belief in localized visual cortical processing. Functional imaging studies of the human brain during vision, initially with positron emission tomography (PET) and more recently with magnetic resonance imaging (MN), have suggested that there are local ‘hot spots’ of neural activity, which can be found in slightly different cortical locations depending on the type of visual stimuli. For instance, hot spots evoked by color stimulation are in a different location from those evoked by visual motion stimulation. And perhaps most interestingly, the location of the hot spot found during color stimulation is close to the brain area in which localized lesions cause achromatopsia [ 561, whereas the hot spot produced by visual motion stimulation is close to @ Current
Biology
the region implicated in motion deficits 161. These results, and others like them, suggest that there is some regional specialization of the human visual cortex for such dimensions as color, motion, and face recognition. Although these advances are exciting, there remains a general consensus that human studies of cortical localization leave a lot to be desired - because virtually nothing is known about the connectional anatomy and single cell physiology of human cortex (nor is it likely that this will change), and because human cortical lesions are hopelessly clumsy: they are not confined to known structures, are not made with axon-sparing methods, and cannot involve ‘pre’ and ‘post’ comparisons in which measurements are taken from normal tissue before the lesion occurs, AI-I obvious solution to these problems is to compare these findings from humans with the wealth of experimental data from non-human primates, primarily macaque monkeys. Indeed, the macaque monkey offers just the sort of information that is not available for human visual cortex. Macaque cortex has been mapped connectionally [7] in somewhat dizzying detail. What is more, there is a great wealth of data from recording single neurones that can be used to flesh out anatomical maps. Beyond these obvious advantages, macaques offer many sorts of experimental information that are not even potentially available from humans - studies of the effects on the developing visual system of rearing in visually restricted environments, current source density analysis (the study of sources and sinks of electrical activity in the brain), and deoxyglucose mapping of metabolically active areas, to name a few. All of these information sources would become very useful if the macaque could be shown to be an informative model for the function of the human visual system. As might be expected, given the potential benefits, the literature is rich with proposed parallels between macaque and human visual cortices. One of the first similarities to be suggested, and one that continues to arouse speculation, is between the regions involved in the processing of visual motion - a small myelinated region of lateral human cortex and a region of the macaque extrastriate area known as MT. This match relies, on the human side, on functional imaging of the hot spot in the brain found with visual motion stimulation and the locus of brain lesions that cause deficits in human motion perception, On the macaque side, the physiological properties of MT neurons are motion-dominated and a deficit in macaque motion perception is caused by MT lesions. This proposed match is the most plausible of those suggested to date, but many investigators think that even this parallel will prove ephermeral. 1993,
Vol 3 No 4
DISPATCH
Macaque
Sagittal
Human
-----
Transverse
Fig. 1. Coronal, sagittal and transverse views of the brains of macaque (left) and human (right). The two brains are shown at different magnifications as the human brain is much larger. In the maca ue brain, the mid-blue regions indicate the extent of area V4, all of which was iesiones in V4 in the study of Heywood et al., [I]. The 1 ark blue region shows the site of a more restricted V4 lesion that can be used when fixation locus is controlled during visual testing (e.g. in the study of Schiller and Lee, [Ill). In the human brain, the three views illustrate in red the locus of the imaging hot spot found by Zeki et al. [61 in response to color-varying visual stimulation, The locus of lesions that result in cerebral achromato sia [4] are indicated in mid-blue and can only be estimated as there are no anatomical data for this part of the human brain that coul dpsuggest a candidate area for V4.
A more recent match, on which I shall focus, and on which the Heywood et al. [l] paper casts some light, is the ‘human V4’ proposal, This terminology reflects the attempt to combine macaque single-unit physiology from area V4 with human achromatopsia, in order to
deftne a single area in the visual cortexof these two primates that is central to the visual processing of color, The investigator most identified with this approach is Semir Zeki of University College, Iondon, who has conducted many of the physiological studies that have ledto the identification
227
228
Current
Biology
1993, Vol 3 No 4
of macaque ~4 as a color-specialized area. Perhaps his most dramatic iindings have concerned the response of neurons in V4, not to the wavelength (actual color) of the stimuli, but to their ‘contextual color’ when presented within an array of colored patches 181. Humans, like single neurons in macaques, respond to colors in a contextual or opponent fashion (i.e responding to the difference between a color and its background), suggesting that this neuronal response may be particularly critical for color perception. Zeki has proposed that the relatively specific decolorization of the visual world found in cerebral achromatopsia may result from damage to the human counterpart of the cortical area V4 in the macaque [4]. In the study by Heywood et al. [ 11, a broad range of visual abilities, with particular emphasis on color vision, was tested in three macaques before and after bilateral lesions were made in cortical area V4 (Fig. 1). This was not the first time that macaques have been tested visually after ~4 lesions. At least four groups have published such studies [!+12], and the general consensus that has emerged from this work is that macaques retain rather good color vision after ~4 lesions. Unfortunately, one cannot ask these monkeys if the world appears decolorized, one of the major changes reported by human achromatopsics, but it should be possible to see if they show the same color threshold losses as their human counterparts. What was most interesting about the recent Heywood et al. [ 1] study was that it was designed to see if macaques without V4 had similar deficits to those found in the color vision of a human achromatopsic they had previously examined [ 131. The most striking loss in their achromatopsic patient (and in many previously reported patients) was in his ability to make color-discriminations, shown most drastically by his abysmal performance on a color sorting task, known as the FarnsworthMunsell loo-Hue Test, with 13 mm desaturated (i.e. pale) color caps. The patient’s poor performance was also repeated in ordering and oddity discrimination tasks with larger color patches, and with color patches of graded saturation. Heywood and colleagues then adapted the stimuli of this study to test the color vision of their monkeys after lesions in the V4 region. Unlike the human patient, the monkeys showed excellent performance on the threechoice oddity tasks for color discrimination. They were also able to do two tasks that required the discrimination of ordered from disordered series of colored patches, al though they made a moderate number of errors before reaching the ‘85% correct’ performance criterion. Unfortunately, the authors were unable to train the experimental and control monkeys on an additional ordering task, designed as an analogue of the Farnsworth-Munsell Test, in which the color patches were separated by an achromatic background. However, despite this limitation on the monkey-human comparison, this study shows quite convincingly that monkeys with V4 lesions show little or no impairment on color-discrimination tasks that are impossible for a human achromatopsic. This study strengthens the emerging conclusion that in color vision, as in motion perception and in visual neglect, macaques with cortical lesions do not seem to show
the profound and enduring visual loss found in some humans. To be sure, there are persistent effects of cortical lesions in macaques, such as marginal abnormalities in eye movements, slight limitations in texture perception, and increases in the number of trials needed to learn form discriminations. However, none of these is as fundamental or as dramatic as the color vision and motion perception weaknesses of human patients. An important difference may be the extent to which the lesions are localized. In many human cases, the damage appears to extend well below the cortical mantle and deep into the fiber tracts underlying the grey matter. Of course, some experimental lesions made in macaques also damage white matter, if they are not produced with an axon-sparing toxicant such as ibotenic acid. But such damage usually does not extend as deep into white matter as that caused by strokes or the excision of epileptic foci. Whether or not a different location is the basis, however, the lack of permanent and dramatic visual losses seen in experimental macaques does not support the notion of specific, modular processing units in primate visual cortex. On the other hand, as pointed out above, imaging studies in humans show local hot spots of cortical activity in response to color or visual motion stimulation. Is this not strong evidence of localized cortical processing? It certainly appears to suggest modular function, especially if the hot spots are located in regions of cortical grey matter that might correspond to visual areas in the macaque. Even so, it is not clear that the hot spots are well placed to correspond to visual areas. For exam ple, in a recent study [6] of a hot spot responsive to color stimulation, the focus of activity was found sufficiently distant from the cortical surface that it might be in the white matter (Fig. l), although one cannot be certain, given that the sulcal fold pattern in these subjects is not known. Is this a matter of slight mislocalization of the hot spot, or an indication that it is not the cortical areas themselves that show specialization but rather regions of intracortical connection? A second concern is that the hot spots are the result of image processing, which could turn simple, intensive non-linearities in signal distribution into apparently local ized activity. Many cortical areas are active during visual stimulation, but this general activity is removed by the subtraction of activity that is common to other forms of stimulation from that due to the stimulation of interest. Thus, the colorful areas pinpointed in these studies are the areas that show increased activity during particular types of visual stimulation relative to other types of visual stimulation, One would expect that the activity in the marked areas increases more than that in other regions, but this is not necessarily the case. If there were an accelerating, non-linearity in the function relating cortical activity to the amount of PET or MRI signal (that is, if there were a selective amplification of high signals relative to the background activity), then subtraction would highlight regions of peak activity but would not indicate how widespread the regions were. Of course, this type of widespread pattern might be exactly what we would expect of even a modularly organized visual cortex, as multiple modules might be simultaneously activated by
DISPATCH
many types of stimulation. The greater difhculty is to be certain that this is not the response signature of a cortex with a more distributed representation of visual function. It is of some concern that even if the cortex had a non-modular organization, hot spots might be created by subtraction of images taken with and without stimulation. Finally, if macaque and human cortices are not organized differently, one is left with the difhculty of understanding how humans could lose particular visual functions af ter naturally occurring cortical lesions. Two possibilities come to mind. The first is that there could be greater selectivity to lesions in the visual cortex than is suggested by their position rather deep within the cortex. Selectivity, despite this deep location, could come about if there were some special vulnerability of particular neural elements, for example sensitivity of finer axons, transmitter-specific ischaemic damage and specific effects on certain receptor types, or even fortuitous damage to specialized axon bun dles passing through a region. This speculation recalls the well established observation that orientation-specific loss of contrast sensitivity can be caused by multiple sclerosis, a disease that affects axonal myelin [ 141, and that this peculiar visual loss most likely reflects damage in the visual cortex - the region in which orientation specificity is first found in macaques. A less attractive possible explanation of function-specific loss after human cortical lesions is that the cortical damage may be truly random but that in some cases non-specific damage may result in very specific visual loss. A possible example is the intriguing case of a rather specific inability to perform visually guided movements following probably widespread brain damage from carbon monoxide poisoning [ 151. The next few years are likely to bring advances in imaging techniques, further studies of humans with cortical lesions, and continued experimental studies with macaques, like those of Heywood and colleagues [l,lO] , which may bring the human and macaque findings into register. Until then, the description of human V4 must remain more hypothesis than conclusion. References 1. HI??OOD
CA
GAXXTI
A, COWEY
A Cortical
area
V4 and
its
role
2.
in the perception
of color.
J Neurosci
229
1992, 12:40564065. of movedamage Brain 1991,
ZIHL J, VON CRAMPON D, MAI N, SCH~UD CH: Disturbance
ment
vision
after
bilateral
posterior
brain
114:223$2252. 3. 4. 5.
AR, DAMA%O H, VAN HOESEN GW: anatomic basis and behavioral mechanisms 32:331-341. ZEKI S: A century of cerebral achromatopsia 1131721-1777. CORSE’ITA M, MIFXN
ZEKI
S, WA’IXON
8. 9. 10.
Bruin
1998,
attention during speed: functional / Neurasci 1991,
JDG,
LUECK
CJ,
visual discriminations anatomy by positron 11:2383-2402.
FFUSTON
KJ,
KENNARD
C,
RSJ: A direct
demonstration of functional specialization in human visual cortex. J Neurasci 1991, 11:641&9. FELLEMAN DJ, VAN ESSEN DC: Distributed hierarchical processing in the primate cerebral cortex. Cerebral Cortex 1991, 1:147. ZEKI S: Colour coding in the cerebral cortex: the reaction of cells in monkey visual cortex to wavelengths and colours. Neumcience 1983, 9741-765. DEAN P: Visual cortex ablation and thresholds for successively presented stimuli in rhesus monkeys: II. Hue. Exp Bruin Res 1991, 35:6%33. FRACKOWIAK
7.
Neurohgy
FM, DOBMEY!ZR S, SHULMAN GL, PETEF~EN SE:
Selective and divided of shape, color, and emission tomography
6.
Prosopagnosia 1982,
DAMA%O
HEYw~OD
the
CA,
COWEY
discrimination
A: On
of hue
the
role
and pattern
of
cortical
in macaque
area
V4
in
monkeys.
J Neurosci 1987, 7:2601-2617. 11.
SCHILLER PH,
V4 in vision. 12.
13.
14.
LEE K: The role of the primate Science 1991, 251:1251-1253.
area
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William H. Merigan, Department of Ophthalmology and Center for Visual Science, Box 314, University of Rochester, Rochester, NY 14642, USA